ArticleStem cell research & therapy2022
Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Engineering Smart Biomaterial Interfaces for iPSC-CM Maturation: A Biophysical and Metabolic Reprogramming Approach to Regenerative Cardiac Medicine.International journal of molecular sciences · 2026Review
- EV-Encapsulated Mitochondrial miRNAs: Enhancing Cardiomyocyte Bioenergetics.International journal of molecular sciences · 2026Review
- Microglia derived from human induced pluripotent stem cells are regulated by osteopontin, an endogenous extracellular matrix protein maintaining immune homeostasis.Frontiers in neuroscience · 2026Article
- Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy.Apoptosis : an international journal on programmed cell death · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Pluripotent stem cell-derived cardiomyocyte transplantation: marching from bench to bedside.Science China. Life sciences · 2025Review
- Uncovering cell type-specific phenotypes using a novel human in vitro model of transthyretin amyloid cardiomyopathy.Stem cell research & therapy · 2025Article
- Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches.Biophysical reviews · 2025Review
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- Integrating Prime Editing and Cellular Reprogramming as Novel Strategies for Genetic Cardiac Disease Modeling and Treatment.Current cardiology reports · 2024Review
- Label-Free Raman Spectroscopy for Assessing Purity and Maturation of hiPSC-Derived Cardiac Tissue.Analytical chemistry · 2024Article
- iPSC-Derived Cardiomyocytes as a Disease Model to Understand the Biology of Congenital Heart Defects.Cells · 2024Review
- Ferroptosis in diabetic cardiomyopathy: Advances in cardiac fibroblast-cardiomyocyte interactions.Heliyon · 2024Review
- Article
- Advances in induced pluripotent stem cell-derived cardiac myocytes: technological breakthroughs, key discoveries and new applications.The Journal of physiology · 2024Review
- Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs.Biomaterials science · 2024Article
- Independent compartmentalization of functional, metabolic, and transcriptional maturation of hiPSC-derived cardiomyocytes.Cell reports · 2024Article
- Uncovering the Genetic Basis of Congenital Heart Disease: Recent Advancements and Implications for Clinical Management.CJC pediatric and congenital heart disease · 2023Review
- Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) do not display all hallmarks of mature primary cardiomyocytes, especially the ability to use fatty acids (FA) as an energy source, containing high mitochondrial mass, presenting binucleation and increased DNA content per nuclei (polyploidism), and synchronized electrical conduction. This immaturity represents a bottleneck to their application in (1) disease modelling-as most cardiac (genetic) diseases have a middle-age onset-and (2) clinically relevant models, where integration and functional coupling are key. So far, several methods have been reported to enhance iPSC-CM maturation; however, these protocols are laborious, costly, and not easily scalable. Therefore, we developed a simple, low-cost, and rapid protocol to promote cardiomyocyte maturation using two small molecule activators of the peroxisome proliferator-activated receptor β/δ and gamma coactivator 1-alpha (PPAR/PGC-1α) pathway: asiatic acid (AA) and GW501516 (GW). METHODS AND
resultsMonolayers of iPSC-CMs were incubated with AA or GW every other day for ten days resulting in increased expression of FA metabolism-related genes and markers for mitochondrial activity. AA-treated iPSC-CMs responsiveness to the mitochondrial respiratory chain inhibitors increased and exhibited higher flexibility in substrate utilization. Additionally, structural maturity improved after treatment as demonstrated by an increase in mRNA expression of sarcomeric-related genes and higher nuclear polyploidy in AA-treated samples. Furthermore, treatment led to increased ion channel gene expression and protein levels.
conclusionsCollectively, we developed a fast, easy, and economical method to induce iPSC-CMs maturation via PPAR/PGC-1α activation. Treatment with AA or GW led to increased metabolic, structural, functional, and electrophysiological maturation, evaluated using a multiparametric quality assessment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.